Decrypting the crosstalk of noncoding RNAs in the progression of IPF

Wang, Yujuan; Han, Xiao; Zhao, Fangyuan; Han, Lei; Gao, Rong; Yan, Bingdi; Ren, Jin; Yang, Junling

doi:10.1007/s11033-020-05368-9

Cited by 8 publications

(9 citation statements)

References 97 publications

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“…We also checked the data for expression of characteristic miRNAs associated with specific pathological condition. Major miRNAs described in idiopathic pulmonary fibrosis with putative functions in aberrant inflammatory responses and in regulation of extra cellular matrix synthesis, collagen expression, matrix metalloproteases (MMP) expression and epithelial-mesenchymal transition [ 25 , 27 , 36 , 37 ] such as let-7d, miR-145, miR-199, miR-200b/c, miR-21, miR-26a, miR-29a/c and miR-92a (and several others, see Additional file 4 : Table S3) could be detected in human PCLS. miRNAs such as miR-125a/b, miR-145/146a, miR-149, miR-15b and miR-199a (Additional file 4 : Table S3) are described as mediators of the TGFß signaling cascade and of genes with impact on the development and progression of COPD, inflammatory response, and airway epithelial repair after injury.…”

Section: Main Textmentioning

confidence: 99%

“…Some RNA therapeutics have been approved or in phase III trials [ 21 ]. Accumulating number of investigations show a pivotal role of miRNAs in the pathogenesis of respiratory diseases such as fibrosis, asthma or chronic obstructive pulmonary disease (COPD) [ 22 – 27 ]. Given these central role of miRNAs in lung diseases, they are candidates for prognostic or therapeutic biomarkers and novel therapeutic approaches.…”

Section: Introductionmentioning

confidence: 99%

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A modified protocol for successful miRNA profiling in human precision-cut lung slices (PCLS)

et al. 2021

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Objective Human precision cut lung slices (PCLS) are widely used as an ex vivo model system for drug discovery and development of new therapies. PCLS reflect the functional heterogeneity of lung tissue and possess relevant lung cell types. We thus determined the use of PCLS in studying non-coding RNAs notably miRNAs, which are important gene regulatory molecules. Since miRNAs play key role as mediators of respiratory diseases, they can serve as valuable prognostic or diagnostic biomarkers, and in therapeutic interventions, of lung diseases. A technical limitation though is the vast amount of agarose in PCLS which impedes (mi)RNA extraction by standard procedures. Here we modified our recently published protocol for RNA isolation from PCLS to enable miRNA readouts. Results The modified method relies on the separation of lysis and precipitation steps, and a clean-up procedure with specific magnetic beads. We obtained successfully quality miRNA amenable for downstream applications such as RTqPCR and whole transcriptome miRNA analysis. Comparison of miRNA profiles in PCLS with published data from human lung, identified all important miRNAs regulated in IPF, COPD, asthma or lung cancer. Therefore, this shows suitability of the method for analyzing miRNA targets and biomarkers in the valuable human PCLS model.

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Section: Main Textmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A modified protocol for successful miRNA profiling in human precision-cut lung slices (PCLS)

et al. 2021

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“…We also checked the data for expression of characteristic miRNAs associated with specific pathological condition. Major miRNAs described in idiopathic pulmonary fibrosis with putative functions in aberrant inflammatory responses and in regulation of extra cellular matrix synthesis, collagen expression, matrix metalloproteases (MMP) expression and epithelial-mesenchymal transition [25,27,36,37] such as let-7d, miR-145, miR-199, miR-200b/c, miR-21, miR-26a, miR-29a/c and miR-92a (and several others, see Table S3) could be detected in human PCLS. miRNAs such as miR-125a/b, miR-145/146a, miR-149, miR-15b and miR-199a (Table S3) are described as mediators of the TGFß signaling cascade and of genes with impact on the development and progression of COPD, inflammatory response, and airway epithelial repair after injury.…”

Section: Genome-wide Mirna Profiling In Human Pcls and Detection Of Cmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

miRNA Profiling in Human Precision-cut Lung Slices (PCLS))

Niehof

Reamon-Buettner

Danow

et al. 2021

Preprint

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ObjectiveHuman precision cut lung slices (PCLS) are widely used as an ex vivo model system for drug discovery and development of new therapies. PCLS reflect the functional heterogeneity of lung tissue and possess relevant lung cell types. We thus determined the use of PCLS in studying non-coding RNAs notably miRNAs, which are important gene regulatory molecules. Since miRNAs play key role as mediators of respiratory diseases, they can serve as valuable prognostic or diagnostic biomarkers, and in therapeutic interventions, of lung diseases. A technical limitation though is the vast amount of agarose in PCLS which impedes (mi)RNA extraction by standard procedures. Here we modified our recently published protocol for RNA 29 isolation from PCLS to enable miRNA readouts. Results The modified method relies on the separation of lysis and precipitation steps, and a clean-up procedure with specific magnetic beads. We obtained successfully quality miRNA amenable for downstream applications such as RTqPCR and whole transcriptome miRNA analysis. Comparison of miRNA profiles in PCLS with published data from human lung, identified all important miRNAs regulated in IPF, COPD, asthma or lung cancer. Therefore, this shows suitability of the method for analyzing miRNA targets and biomarkers in the valuable human 38 PCLS model.

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“…LncRNA sirt1 antisense was reported to inhibit TGF-β1-mediated epithelial-mesenchymal transition in vitro and alleviate the progression of IPF in vivo 16 . Crosstalk among non-coding RNAs plays a crucial regulatory role in the progression of IPF 17 . Savary et al demonstrated that lncRNA DNM3OS regulates myofibroblast activation by giving rise to profibrotic mature miRNAs, such as miR-199a-5p/3p and miR-214-3p 18 .…”

Section: Introductionmentioning

confidence: 99%

LncRNA CTD-2528L19.6 prevents the progression of IPF by alleviating fibroblast activation

et al. 2021

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Long non-coding RNAs (lncRNAs) have emerged as critical factors for regulating multiple biological processes during organ fibrosis. However, the mechanism of lncRNAs in idiopathic pulmonary fibrosis (IPF) remains incompletely understood. In the present study, two sets of lncRNAs were defined: IPF pathogenic lncRNAs and IPF progression lncRNAs. IPF pathogenic and progression lncRNAs-mRNAs co-expression networks were constructed to identify essential lncRNAs. Network analysis revealed a key lncRNA CTD-2528L19.6, which was up-regulated in early-stage IPF compared to normal lung tissue, and subsequently down-regulated during advanced-stage IPF. CTD-2528L19.6 was indicated to regulate fibroblast activation in IPF progression by mediating the expression of fibrosis related genes LRRC8C, DDIT4, THBS1, S100A8 and TLR7 et al. Further studies showed that silencing of CTD-2528L19.6 increases the expression of Fn1 and Collagen I both at mRNA and protein levels, promoted the transition of fibroblasts into myofibroblasts and accelerated the migration and proliferation of MRC-5 cells. In contrast, CTD-2528L19.6 overexpression alleviated fibroblast activation in MRC-5 cells induced by TGF-β1. LncRNA CTD-2528L19.6 inhibited fibroblast activation through regulating the expression of LRRC8C in vitro assays. Our results suggest that CTD-2528L19.6 may prevent the progression of IPF from early-stage and alleviate fibroblast activation during the advanced-stage of IPF. Thus, exploring the regulatory effect of lncRNA CTD-2528L19.6 may provide new sights for the prevention and treatment of IPF.

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Decrypting the crosstalk of noncoding RNAs in the progression of IPF

Cited by 8 publications

References 97 publications

A modified protocol for successful miRNA profiling in human precision-cut lung slices (PCLS)

A modified protocol for successful miRNA profiling in human precision-cut lung slices (PCLS)

miRNA Profiling in Human Precision-cut Lung Slices (PCLS))

LncRNA CTD-2528L19.6 prevents the progression of IPF by alleviating fibroblast activation

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